Wafer-scale assembly of insulator-membrane-insulator devices for nanopore sensing

Abstract

Described herein are nanopore devices as well as methods for assembling a nanopore device including one or more nanopores that can be used to detect molecules such as nucleic acids, amino acids (proteins), and the like. Specifically, a nanopore device includes an insulating layer that reduces electrical noise and thereby improves the sensing resolution of the one or more nanopores integrated within the nanopore device.

The invention claimed is: 
     
       1. A system comprising:
 a nanopore device comprising: 
 a substrate comprising one or more fluid channels; 
 a cover comprising a center hole and a plurality of outer holes; and 
 a membrane layer positioned between the substrate and the cover, a first surface of the membrane layer bonded to the surface of the substrate, the membrane layer comprising: 
 one or more nanopores that each fluidically connects one of the one or more fluid channels of the substrate to the center hole of the cover, and 
 a plurality of holes aligned with the plurality of outer holes of the cover; and 
 a flow-cell housing configured to affix a position of the nanopore device relative to the flow-cell housing. 
 
     
     
       2. The system of  claim 1 , wherein the flow-cell housing comprises a plurality of sealable ports, each sealable port configured to substantially align with one of the center hole or the plurality of outer holes of the cover. 
     
     
       3. The system of  claim 1 , wherein the flow-cell housing comprises an electrode residing within a reservoir of one of the one or more fluid channels in the nanopore device. 
     
     
       4. The system of  claim 3 , wherein the electrode is in contact with a conductive trace coupled to the flow-cell housing. 
     
     
       5. The system of  claim 1 , wherein the flow-cell housing further comprises an aperture configured to receive an optical imaging device. 
     
     
       6. The system of  claim 1 , wherein the flow-cell housing further comprises an inlet configured to transmit a flow under pressure to one of the one or more fluid channels of the nanopore device. 
     
     
       7. The system of  claim 1 , wherein the flow-cell housing comprises a cavity in fluid connection with one of the one or more fluid channels of the nanopore device. 
     
     
       8. A system comprising:
 a nanopore device comprising: 
 a substrate comprising one or more fluid channels; 
 a cover comprising a center hole and a plurality of outer holes; and 
 a membrane layer positioned between the substrate and the cover, a first surface of the membrane layer bonded to the surface of the substrate, the membrane layer comprising: 
 one or more nanopores that each fluidically connects one of the one or more fluid channels of the substrate to the center hole of the cover, and 
 a plurality of holes aligned with the plurality of outer holes of the cover, wherein the membrane layer comprises a first portion that has a first thickness and a second portion that has a second thickness. 
 
     
     
       9. The system of  claim 8 , wherein the second portion has a second thickness that is less than the first thickness. 
     
     
       10. The system of  claim 8 , wherein the second portion of the membrane is located above a portion of the one or more fluid channels. 
     
     
       11. The system of  claim 8 , wherein the first portion of the membrane layer has a thickness between 100-300 nm and wherein the second portion of the membrane layer has a thickness between 10-50 nm. 
     
     
       12. The system of  claim 8 , wherein each of one or more nanopores is positioned at the second portion of the membrane layer. 
     
     
       13. The system of  claim 8 , wherein the nanopore device further comprises a second membrane layer coupled to the cover, the second membrane layer comprising a fluid channel and a nanopore located in the fluid channel of the second membrane, the nanopore of the second membrane being substantially aligned with one of the one or more nanopores of the membrane layer. 
     
     
       14. A system comprising:
 a nanopore device comprising: 
 a substrate comprising one or more fluid channels; 
 a cover comprising a center hole and a plurality of outer holes; and 
 a membrane layer positioned between the substrate and the cover, a first surface of the membrane layer bonded to the surface of the substrate, the membrane layer comprising: 
 one or more nanopores that each fluidically connects one of the one or more fluid channels of the substrate to the center hole of the cover, and 
 a plurality of holes aligned with the plurality of outer holes of the cover, wherein a first nanopore of the one or more nanopores fluidically connects a first fluid channel of the substrate to the center hole of the cover and a second nanopore of the one or more nanopores fluidically connects a second fluid channel of the substrate to the center hole of the cover. 
 
     
     
       15. The system of  claim 14 , wherein a portion of a first fluid channel and a portion of the second fluid channel are parallel to each other. 
     
     
       16. The system of  claim 14 , wherein at least one of the first fluid channel and second fluid channel forms an elbow point. 
     
     
       17. The system of  claim 16 , wherein the first fluid channel is closest to the second fluid channel at the elbow point. 
     
     
       18. The system of  claim 14 , wherein each of the one or more nanopores is between 5-50 nm in diameter. 
     
     
       19. The system of  claim 14 , wherein one of the one or more fluid channels of the substrate includes a reservoir, and wherein the reservoir is substantially aligned with a hole of the plurality of outer holes of the cover. 
     
     
       20. The system of  claim 14 , wherein the one or more fluid channels of the substrate includes a post.